Pneumolysin will be used as a model for host-mediated pathogenesis in ocular infections involving cytolytic toxins. Toxin-target cell interactions will be studied at the molecular and cellular levels, including: an examination of pneumolysin-stimulated secretion of collagenase by corneal explants, fibroblasts and epithelial cells; of the effects of potential inhibitors on these systems; of a possible role for plasminogen in the pneumolysin stimulation. The function of pneumolysin in the physiology of the pneumococcus will also be studied and the gene encoding pneumolysin will be cloned, permitting evaluation of the role of pneumolysin in virulence, determination of its amino acid sequence, and identification of possible genetic regulatory elements.